Carboxylative Efficacy of Trans and Cis MK7 and Comparison with Other Vitamin K Isomers

Overview

Journal Biofactors

Publisher IOS Press

Specialty Biochemistry

Date 2022 May 18

PMID 35583412

Authors

Ilenia Cirilli

Patrick Orlando

Sonia Silvestri

Fabio Marcheggiani

Phiwayinkosi V Dludla

Nadine Kaesler

Luca Tiano

Affiliations

Soon will be listed here.

Abstract

Carboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ-glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ-carboxyglutamate (Gla) of the vitamin K-dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 (menaquinones, MKs). Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to other trans isomers, it is produced by natural fermentation or chemically in both trans and cis. However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy of trans and cis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla-protein by western blot analysis and using a cell-free system to determine the GGCX activity by HPLC. Trans MK7H showed a higher ability to carboxylate the 70 KDa GLA-protein, previously inhibited in vitro by warfarin treatment. However, cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity of cis MK7H was demonstrated, comparable with both K1H and oxidized trans MK7 but less than trans MK7H . For the first time, a difference of biological activity between cis and trans configuration of menaquinone-7 has been reported.

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